Glycogen metabolism in liver

Protein phosphatases-1, 2 A, 2B, and 2C occur in mammalian liver and, as in skeletal muscle, possess essentially all of the phosphatase activity toward enzymes and regulatory proteins of glycogen metabolism. In liver, however, the ratios of the activities of phosphatase-2A and 2C to that of phosphatase-1 are seven-fold higher than in muscle. Although protein phosphatase-I sediments with glycogen particles in both tissues, a much smaller fraction is glycogen-associated in liver than in muscle. The specific activity of phosphatase-2B is lower in liver than in muscle. Protein phosphatase inhibitors-1 and 2 have been identified in liver, where they appear to function as they do in muscle. A disinhibitor protein (M. W. 9,000) of liver can block the effects of inhibitors-1 and 2 on phosphatase-1. 

Glycogen metabolism in liver is regulated by phosphorylation and dephosphorylation of regulatory and metabolic enzymes. Control of the phosphorylation state is mediated by Ca " ", cAMP, cytosolic glucose concentration, and perhaps, in the case of insulin, by another mechanism. 

Compare the effects of glucagon and epinephrine on glycogen metabolism in liver and in muscle. 

Glucagon Pancreas Stimulates glycogen metabolism in liver... 

Inherited deficiencies in specific enzymes of glycogen metabolism in both liver and muscle are the causes of glycogen storage diseases. 

Bollen M> Keppens S, Stalmans W Specific features of glycogen metabolism in the liver. Biochem J 1998 336 19. 

Glycogen stores in liver and kidney are exhausted in about 24 hours. After this, the body must find glucose equivalents somewhere. The major metabolic adaptations of starvation are the result of having to maintain glucose levels without any direct source of it (Fig. 17-8). 

Mechanism of Action A benzimidazole carbamate anthelmintic that degrades parasite cytoplasmic microtubules, irreversibly blocks cholinesterase secretion, glucose uptake in helminth and larvae (depletes glycogen, decreases ATP production, depletes energy). Vermicidal. Therapeutic Effect Immobilizes and kills worms. Pharmacokinetics Poorly and variably absorbed from GI tract. Widely distributed, cyst fluid and including cerebrospinal fluid (CSF). Protein binding 70%. Extensively metabolized in liver. Primarily excreted in urine and bile. Not removed by hemodialysis. Half-life 8-12 hr. 

Pharmacokinetics Fructose Fructose is slowly absorbed from the Gl tract. Metabolized in liver by phosphorylation and partly converted to liver glycogen and glucose. Excreted in urine. Dextrose Dextrose is rapidly absorbed from Gl tract. Distributed and stored throughout tissues. Metabolized in liver to carbon dioxide and water. 

Stalmans, W., Keppens, S., Bollen, M. (1998) Specific features of glycogen metabolism in the liver. Biochem. J. 336, 19-31. A review that goes into greater depth than this chapter. 

Epinephrine and glucagon have which one of the following effects on glycogen metabolism in the liver ... 

As noted previously, like skeletal muscle, glycogen depletion in liver during endurance exercise is much less in trained animals and in animals who have had free fatty acids artificially elevated. No evidence exists that the mechanism proposed by Randle to account for the inhibition of carbohydrate metabolism in muscle by oxidation of fatty acids is operative in the liver. Thus other factors must be responsible for the slower rate of liver glycogen depletion in these situations. Such factors may include a smaller increase in catecholamine levels, a smaller reduction in insulin levels, and a smaller reduction in blood flow to the liver during exercise (19,20). 

Glycogen Metabolism in the Liver Regulates the Blood-Glucose Level... 

Chart 4 Regulation of glycogen metabolism in mammalian liver. 

A certain person was found to have a defect in glycogen metabolism. The liver of this person could (a) make glucose-6-phosphate from lactate and (b) synthesize glucose-6-phosphate from glycogen but (c) could not synthesize glycogen from glucose-6-phosphate. What enzyme is defective ... 

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